Posttraumatic reduction of edema with aquaporin-4 RNA interference improves acute and chronic functional recovery.

08:00 EDT 31st July 2013 | BioPortfolio

Summary of "Posttraumatic reduction of edema with aquaporin-4 RNA interference improves acute and chronic functional recovery."

Traumatic brain injury (TBI) is common in young children and adolescents and is associated with long-term disability and mortality. The neuropathologic sequelae that result from juvenile TBI are a complex cascade of events that include edema formation and brain swelling. Brain aquaporin-4 (AQP4) has a key role in edema formation. Thus, development of novel treatments targeting AQP4 to reduce edema could lessen the neuropathologic sequelae. We hypothesized that inhibiting AQP4 expression by injection of small-interfering RNA (siRNA) targeting AQP4 (siAQP4) after juvenile TBI would decrease edema formation, neuroinflammation, neuronal cell death, and improve neurologic outcomes. The siAQP4 or a RNA-induced silencing complex (RISC)-free control siRNA (siGLO) was injected lateral to the trauma site after controlled cortical impact in postnatal day 17 rats. Magnetic resonance imaging, neurologic testing, and immunohistochemistry were performed to assess outcomes. Pups treated with siAQP4 showed acute (3 days after injury) improvements in motor function and in spatial memory at long term (60 days after injury) compared with siGLO-treated animals. These improvements were associated with decreased edema formation, increased microglial activation, decreased blood-brain barrier disruption, reduced astrogliosis and neuronal cell death. The effectiveness of our treatment paradigm was associated with a 30% decrease in AQP4 expression at the injection site.Journal of Cerebral Blood Flow & Metabolism advance online publication, 31 July 2013; doi:10.1038/jcbfm.2013.118.


1] Department of Physiology, Loma Linda University, Loma Linda, California, USA [2] Department of Pediatrics, Loma Linda University Medical Center, Loma Linda, California, USA.

Journal Details

This article was published in the following journal.

Name: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
ISSN: 1559-7016


PubMed Articles [14953 Associated PubMed Articles listed on BioPortfolio]

Deletion of aquaporin-4 is neuroprotective during the acute stage of micro traumatic brain injury in mice.

Micro traumatic brain injury (TBI) is the most common type of brain injury, but the mechanisms underlying it are poorly understood. Aquaporin-4 (AQP4) is a water channel expressed in astrocyte end-fee...

Web-based intervention improves social acknowledgement and disclosure of trauma, leading to a reduction in posttraumatic stress disorder symptoms.

This study aims to investigate the effectiveness of web-based intervention on social acknowledgement and disclosure of trauma and to examine the mediating effect of the improvement in social acknowled...

Effect of high-voltage electrical stimulation on the albumin and histamine serum concentrations, edema, and pain in acute joint inflammation of rats.

The mechanism by which high-voltage electrical stimulation (HVPC) acts on edema reduction is unknown.

Dimensional structure and correlates of posttraumatic stress symptoms following suspected acute coronary syndrome.

Posttraumatic stress disorder (PTSD) is a heterogeneous construct, and some have suggested that PTSD triggered by acute coronary syndrome (ACS) may differ from PTSD due to prototypical traumas.

Acute Stress Disorder among Civilians during a War and Posttraumatic Growth Six Years Later: The Impact of Personal and Social Resources.

Various studies suggest a link between stress response to a traumatic event and posttraumatic growth, but little is known about their long-term relationship. In this study, the relationship between ac...

Clinical Trials [5153 Associated Clinical Trials listed on BioPortfolio]

Non Invasive Mechanical Ventilation in Acute Cardiogenic Pulmonary Edema

Cardiogenic pulmonary edema (CPE) is a common medical emergency and noninvasive ventilation (NIV) in addition to conventional medical treatment might be beneficial for patients with CPE.

Evaluation of Inflammatory Symptoms Reduction With Amoxicillin + Ketoprofen in Acute Pharyngeal- Tonsillitis in Pediatric Patients

The purpose of this study is to evaluate the inflammatory symptoms and signs (hyperemia, edema and pain) reduction after 24 hours of treatment with ketoprofen drops when associated to amox...

Treatment of Refractory Diabetic Macular Edema With Infliximab

The purpose of this study is to determine if treatment with infliximab improves macular edema which is refractory to laser photocoagulation in patients with diabetes.

Out-of-Hospital CPAP for Severe Cardiogenic Pulmonary Edema

In cardiogenic pulmonary edema, Continuous Positive Airway Pressure (CPAP) added to medical treatment improves outcome. The present study was designed to assess the benefit of CPAP as a fi...

BK Virus and Renal Dysfunction in Postoperative/Posttraumatic Critically Ill Patients

The purpose of this study is to find out whether acute renal failure is associated with BK virus reactivation in postoperative/posttraumatic critically ill patients with severe SIRS/sepsis...

Medical and Biotech [MESH] Definitions

Aquaporin 2 is a water-specific channel protein that is expressed in KIDNEY COLLECTING DUCTS. The translocation of aquaporin 2 to the apical PLASMA MEMBRANE is regulated by VASOPRESSIN, and MUTATIONS in AQP2 have been implicated in a variety of kidney disorders including DIABETES INSIPIDUS.

Abrupt reduction in kidney function defined as an absolute increase in serum CREATININE of more than or equal to 0.3. mg/dl, a percentage increase in serum creatinine of more than or equal to 50%, or a reduction in urine output. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.

Aquaporin 4 is the major water-selective channel in the CENTRAL NERVOUS SYSTEM of mammals.

Aquaporin 3 is an aquaglyceroporin that is expressed in the KIDNEY COLLECTING DUCTS and is constitutively localized at the basolateral MEMBRANE.

Aquaporin 6 is an aquaglyceroporin that is found primarily in KIDNEY COLLECTING DUCTS. AQP6 protein functions as an anion-selective channel.


Relevant Topics

Anxiety Disorders
Latest News Clinical Trials Research Drugs Reports Corporate
Anxiety is caused by stress. It is a natural reaction, and is beneficial in helping us deal with tense situations and pressure. It is deterimental when is becomes an excessive, irrational dread of everyday situations. The most common types of anxiety di...

Alzheimer's Disease
Latest News Clinical Trials Research Drugs Reports Corporate
Of all the types of Dementia, Alzheimer's disease is the most common, affecting around 465,000 people in the UK. Neurons in the brain die, becuase  'plaques' and 'tangles' (mis-folded proteins) form in the brain. People with Al...

Searches Linking to this Article